| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2023: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2022: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2021: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Outline of Final Research Achievements |
We have now established Chd8 knock-in mice in order to characterize the effects of Chd8 duplication on transcriptional, neuroanatomical, and behavioral phenotypes. We found that Chd8 overexpression impairs the generation of deep-layer neurons in the brain. Transcriptomic analysis showed that Chd8 overexpression alters the expression of genes related to neural development and neuropsychiatric disease, and that the pattern of gene expression in the brain of Chd8 knock-in mice was negatively correlated with that apparent for Chd8 heterozygous mutant mice. Furthermore, behavioral analysis revealed that Chd8 overexpression results in hyperactivity and attenuated anxiety-like behavior, and that these behavioral changes were ameliorated by genetic or pharmacological interventions.
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